A Phase II Trial of Anti-KIR in Smoldering Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01248455
First received: November 24, 2010
Last updated: June 6, 2014
Last verified: May 2014
  Purpose

Background:

  • Recent studies have shown that smoldering multiple myeloma has a high risk of progressing to multiple myeloma, an aggressive type of bone marrow cancer, within 5 years of diagnosis. People with smoldering multiple myeloma have abnormal blood test results that show a high level of M-protein in the blood and of plasma cells in the bone marrow. There are currently no known effective treatments to prevent smoldering multiple myeloma from developing into multiple myeloma, and there are no known tests for determining whether an individual with smoldering multiple myeloma will develop multiple myeloma.
  • Certain cells in the immune system, known as natural killer (NK) cells, are active against multiple myeloma. The experimental drug anti-KIR has been shown to help NK cells kill multiple myeloma cells. Researchers are interested in determining whether anti-KIR can be given to individuals with smoldering multiple myeloma to improve their abnormal blood test results.

Objectives:

- To evaluate the safety and effectiveness of anti-KIR as a treatment for abnormal blood test results related to smoldering multiple myeloma.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with smoldering multiple myeloma.

Design:

  • Participants will be screened with a physical examination and medical history, and will provide baseline blood, urine, and bone marrow samples before beginning the study drug.
  • Participants will receive anti-KIR intravenously for 1 hour, and will be closely monitored for 24 hours after receiving the first dose. If there are no serious side effects, participants will receive five additional anti-KIR doses, one every other month, for a total of six treatment cycles.
  • Participants will have monthly visits to provide additional blood and urine samples, and may have additional bone marrow biopsies as directed by the study researchers.
  • Participants will have followup visits every 3 to 6 months for up to 5 years after receiving anti-KIR treatment.

Condition Intervention Phase
Multiple Myeloma
Myeloma
Smoldering Multiple Myeloma
Drug: (Anti-KIR)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of IPH2101 (Anti-KIR) in Smoldering Multiple Myeloma (SMM)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Response rate [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the toxicity of anti-KIR(IPH2101) in patients with SMM.Evaluate the pharmacokinetic parameters and biological activity of anti-KIR (IPH2101). [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To evaluate the pharmacokinetic parameters and biological activity of anti-KIR(IPH2101). [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: November 2010
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles
Drug: (Anti-KIR)
Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles

Detailed Description:

Background:

  • Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years.
  • Smoldering multiple myeloma (SMM) is a premalignant plasma cell disorder characterized by monoclonal protein greater than or equal to 3 g/dL or bone marrow plasma cells greater than or equal to 10 percent in the absence of myeloma-related tissue impairment with 51 percent progression to MM at 5 years.
  • Current recommendations do not endorse treatment of SMM with chemotherapy.
  • Transplanted Natural Killer (NK) Cells have anti-myeloma activity.
  • Anti-KIR (IPH2101) is a monoclonal antibody that facilitates NK cell mediated killing of myeloma cells by blocking inhibitory receptors (KIR) on NK cells.

Objectives:

  • To assess the response rate of anti-KIR(IPH2101) in patients with SMM
  • To evaluate the toxicity of anti-KIR(IPH2101) in patients with SMM
  • To evaluate the pharmacokinetic parameters and biological activity of anti-KIR (IPH2101)

Eligibility:

  • A confirmed diagnosis of SMM
  • Age greater than or equal to 18 years
  • ECOG performance status in the range of 0-1.
  • Without serious co-morbidity that would interfere with receipt of anti-KIR(IPH2101)

Design:

  • Single-arm Phase II trial of anti-KIR(IPH2101) for patients with SMM.
  • All patients will have initial evaluation and confirmation of diagnosis.
  • Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles.
  • Patients will have routine blood work with SPEP and immunofixation monthly.
  • Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of diagnosis and correlative studies.
  • Patients may donate cellular products or tissues as appropriate for research purposes.
  • Optimal two-stage phase II design will be employed, initially enrolling 9 patients. If 3 or more have a positive outcome, then a total of 21 patients will be enrolled in this study.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Diagnosis of SMM will be made in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group. These criteria include:

    • Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells greater than or equal to 10 percent
    • Absence of anemia: Hemoglobin greater than or equal to 10 g/dl
    • Absence of renal failure: calculated creatinine clearance (according to MDRD) greater than or equal to 40 ml/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
  • Absence of hypercalcemia: Calcium less than or equal to 10.5 mg/dl
  • Absence of lytic bone lesion (skeletal survey)
  • The diagnoses will be confirmed by serum/urine protein electrophoresis, immunofixation and light-chain assays; as well as immunohistochemical analyses of the bone marrow biopsy.
  • Age greater than or equal to 18 years.
  • ECOG performance status of 0-1.
  • Male or female patient who accepts and is able to use recognized effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) through the study and for four months following the final dose of study drug when relevant.
  • The patient must be competent to sign an informed consent form.

EXCLUSION CRITERIA:

  • Patients with a diagnosis of MM or a clinical suspicion of an ongoing progression into full-blown MM
  • Patients without measurable disease defined as serum M-protein less than 1 g/dL.
  • Previous treatment having a proven or potential impact on myeloma cell proliferation or survival (including conventional chemotherapies, immunomodulatory drugs (IMiDs), or proteasome inhibitors).
  • Use of any investigational agent within the last 3 months.
  • Clinical laboratory values at screening:

    • Platelet levels less than 75 times 10(9)/L
    • ANC levels less than 1 times 10(9)/L
    • Bilirubin levels greater than 1.5 ULN ; ALT and AST greater than 3.0 ULN (grade 1 NCI)
  • Primary or associated amyloidosis
  • Known abnormal cardiac status with any of the following:

    • NYHA stage III or IV congestive heart failure
    • Myocardial infarction within the previous 6 months
    • Symptomatic and/or treatment-refractory cardiac arrhythmia. Patients with controlled or asymptomatic arrhythmia are not excluded from this study.
  • Current active infectious disease or positive serology for:

    • Human Immunodeficiency Virus (HIV)
    • Hepatitis C Virus (HCV)
    • Hepatitis B Surface Antigen
  • Severe type of autoimmune disease defined as:

    • One which currently requires or previously required long-term systemic immunosuppressive or immunomodulatory therapy (including corticosteroids, administered by systemic route)
    • And/or it has a substantial probability to cause an irreversible injury to any tissue (e.g. Hashimoto thyroiditis).
    • And/or it is recent or unstable, or has a substantial risk to progress and cause severe complications (e.g. Graves disease)
    • Enrollment of other non severe types of auto-immunes disease requiring topical therapy, or NSAIDS can be considered on a case by case basis by the Principal Investigator.
  • History of a lymphoproliferative malignancy.
  • History of other malignancy (apart from basal cell carcinoma of the skin or in situ cervical carcinoma) except if the patient has been free of symptoms and without active therapy during at least the previous 5 years.
  • Serious concurrent uncontrolled medical disorder.
  • History of allograft or solid organ transplantation.
  • Any psychological or familial condition potentially interfering with compliance with the study protocol and follow-up schedule.
  • Pregnant or lactating women.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01248455

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Mark J Roschewski, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01248455     History of Changes
Other Study ID Numbers: 110024, 11-C-0024
Study First Received: November 24, 2010
Last Updated: June 6, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Monoclonal Antibody
NK Cell Mediated Killing
Response Rate
Pharmacokinetics
Biological Activity
Smoldering Multiple Myeloma
SMM

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 20, 2014